A Critical Role for Induced IgM in the Protection against West Nile Virus Infection

In humans, the elderly and immunocompromised are at greatest risk for disseminated West Nile virus (WNV) infection, yet the immunologic basis for this remains unclear. We demonstrated previously that B cells and IgG contributed to the defense against disseminated WNV infection (Diamond, M.S., B. Shrestha, A. Marri, D. Mahan, and M. Engle. 2003. J. Virol. 77:2578–2586). In this paper, we addressed the function of IgM in controlling WNV infection. C57BL/6J mice (sIgM−/−) that were deficient in the production of secreted IgM but capable of expressing surface IgM and secreting other immunoglobulin isotypes were vulnerable to lethal infection, even after inoculation with low doses of WNV. Within 96 h, markedly higher levels of infectious virus were detected in the serum of sIgM−/− mice compared with wild-type mice. The enhanced viremia correlated with higher WNV burdens in the central nervous system, and was also associated with a blunted anti-WNV IgG response. Passive transfer of polyclonal anti-WNV IgM or IgG protected sIgM−/− mice against mortality, although administration of comparable amounts of a nonneutralizing monoclonal anti-WNV IgM provided no protection. In a prospective analysis, a low titer of anti-WNV IgM antibodies at day 4 uniformly predicted mortality in wild-type mice. Thus, the induction of a specific, neutralizing IgM response early in the course of WNV infection limits viremia and dissemination into the central nervous system, and protects against lethal infection

Investigating Financial Incentives for Maternal Health: An Introduction

Projection of current trends in maternal and neonatal mortality reduction shows that many countries will fall short of the UN Millennium Development Goal 4 and 5. Underutilization of maternal health services contributes to this poor progress toward reducing maternal and neonatal morbidity and mortality. Moreover, the quality of services continues to lag in many countries, with a negative effect on the health of women and their babies, including deterring women from seeking care. To enhance the use and provision of quality maternal care, countries and donors are increasingly using financial incentives. This paper introduces the JHPN Supplement, in which each paper reviews the evidence of the effectiveness of a specific financial incentive instrument with the aim of improving the use and quality of maternal healthcare and impact. The US Agency for International Development and the US National Institutes of Health convened a US Government Evidence Summit on Enhancing Provision and Use of Maternal Health Services through Financial Incentives on 24-25 April 2012 in Washington, DC. The Summit brought together leading global experts in finance, maternal health, and health systems from governments, academia, development organizations, and foundations to assess the evidence on whether financial incentives significantly and substantially increase provision, use and quality of maternal health services, and the contextual factors that impact the effectiveness of these incentives. Evidence review teams evaluated the multidisciplinary evidence of various financial mechanisms, including supply-side incentives (e.g. performance-based financing, user fees, and various insurance mechanisms) and demand-side incentives (e.g. conditional cash transfers, vouchers, user fee exemptions, and subsidies for care-seeking). At the Summit, the teams presented a synthesis of evidence and initial recommendations on practice, policy, and research for discussion. The Summit enabled structured feedback on recommendations which the teams included in their final papers appearing in this Supplement. Papers in this Supplement review the evidence for a specific financial incentive mechanism (e.g. pay for performance, conditional cash transfer) to improve the use and quality of maternal healthcare and makes recommendations for programmes and future research. While data on programmes using financial incentives for improved use and indications of the quality of maternal health services support specific conclusions and recommendations, including those for future research, data linking the use of financial incentives with improved health outcomes are minimal

Evidence Acquisition and Evaluation for Evidence Summit on Enhancing Provision and Use of Maternal Health Services through Financial Incentives

Recognizing the need for evidence to inform US Government and governments of the low- and middleincome countries on efficient, effective maternal health policies, strategies, and programmes, the US Government convened the Evidence Summit on Enhancing Provision and Use of Maternal Health Services through Financial Incentives in April 2012 in Washington, DC, USA. This paper summarizes the background and methods for the acquisition and evaluation of the evidence used for achieving the goals of the Summit. The goal of the Summit was to obtain multidisciplinary expert review of literature to inform both US Government and governments of the low- and middle-income countries on evidence-informed practice, policies, and strategies for financial incentives. Several steps were undertaken to define the tasks for the Summit and identify the appropriate evidence for review. The process began by identifying focal questions intended to inform governments of the low-and middle-income countries and the US Government about the efficacy of supply- and demand-side financial incentives for enhanced provision and use of quality maternal health services. Experts were selected representing the research and programme communities, academia, relevant non-governmental organizations, and government agencies and were assembled into Evidence Review Teams. This was followed by a systematic process to gather relevant peer-reviewed literature that would inform the focal questions. Members of the Evidence Review Teams were invited to add relevant papers not identified in the initial literature review to complete the bibliography. The Evidence Review Teams were asked to comply with a specific evaluation framework for recommendations on practice and policy based on both expert opinion and the quality of the data. Details of the search processes and methods used for screening and quality reviews are described

The effect of intranasal insulin on appetite and mood in women with and without obesity: an experimental medicine study

Background/Objectives Intranasal (IN) administration of insulin decreases appetite in humans, but the underlying mechanisms are unclear, and it is unknown whether IN insulin affects the food intake of women with obesity. Subjects/Methods In a double-blind, placebo-controlled, crossover design, participants (35 lean women and 17 women with obesity) were randomized to receive 160 IU/1.6 mL of IN insulin or placebo in a counterbalanced order in the post prandial state. The effects of IN insulin on cookie intake, appetite, mood, food reward, cognition and neural activity were assessed. Results IN insulin in the post prandial state reduced cookie intake, appetite and food reward relative to placebo and these effects were more pronounced for women with obesity compared with lean women. IN insulin also improved mood in women with obesity. In both BMI groups, IN insulin increased neural activity in the insula when viewing food pictures. IN insulin did not affect cognitive function. Conclusions These results suggest that IN insulin decreases palatable food intake when satiated by reducing food reward and that women with obesity may be more sensitive to this effect than lean women. Further investigation of the therapeutic potential of IN insulin for weight management in women with obesity is warranted

A Taxonomy and Results from a Comprehensive Review of 28 Maternal Health Voucher Programmes

It is increasingly clear that Millennium Development Goal 4 and 5 will not be achieved in many low- and middle-income countries with the weakest gains among the poor. Recognizing that there are large inequalities in reproductive health outcomes, the post-2015 agenda on universal health coverage will likely generate strategies that target resources where maternal and newborn deaths are the highest. In 2012, the United States Agency for International Development convened an Evidence Summit to review the knowledge and gaps on the utilization of financial incentives to enhance the quality and uptake of maternal healthcare. The goal was to provide donors and governments of the low- and middle-income countries with evidenceinformed recommendations on practice, policy, and strategies regarding the use of financial incentives, including vouchers, to enhance the demand and supply of maternal health services. The findings in this paper are intended to guide governments interested in maternal health voucher programmes with recommendations for sustainable implementation and impact. The Evidence Summit undertook a systematic review of five financing strategies. This paper presents the methods and findings for vouchers, building on a taxonomy to catalogue knowledge about voucher programme design and functionality. More than 120 characteristics under five major categories were identified: programme principles (objectives and financing); governance and management; benefits package and beneficiary targeting; providers (contracting and service pricing); and implementation arrangements (marketing, claims processing, and monitoring and evaluation). Among the 28 identified maternal health voucher programmes, common characteristics included: a stated objective to increase the use of services among the means-tested poor; contracted-out programme management; contracting either exclusively private facilities or a mix of public and private providers; prioritizing community-based distribution of vouchers; and tracking individual claims for performance purposes. Maternal voucher programmes differed on whether contracted providers were given training on clinical or administrative issues; whether some form of service verification was undertaken at facility or communitylevel; and the relative size of programme management costs in the overall programme budget. Evidence suggests voucher programmes can serve populations with national-level impact. Reaching scale depends on whether the voucher programme can: (i) keep management costs low, (ii) induce a large demand-side response among the bottom two quintiles, and (iii) achieve a quality of care that translates a greater number of facility-based deliveries into a reduction in maternal morbidity and mortality

Financial Incentives and Maternal Health: Where Do We Go from Here?

Health financing strategies that incorporate financial incentives are being applied in many low- and middle-income countries, and improving maternal and neonatal health is often a central goal. As yet, there have been few reviews of such programmes and their impact on maternal health. The US Government Evidence Summit on Enhancing Provision and use of Maternal Health Services through Financial Incentives was convened on 24-25 April 2012 to address this gap. This article, the final in a series assessing the effects of financial incentives\u2014performance-based incentives (PBIs), insurance, user fee exemption programmes, conditional cash transfers, and vouchers\u2014summarizes the evidence and discusses issues of context, programme design and implementation, cost-effectiveness, and sustainability. We suggest key areas to consider when designing and implementing financial incentive programmes for enhancing maternal health and highlight gaps in evidence that could benefit from additional research. Although the methodological rigor of studies varies, the evidence, overall, suggests that financial incentives can enhance demand for and improve the supply of maternal health services. Definitive evidence demonstrating a link between incentives and improved health outcomes is lacking; however, the evidence suggests that financial incentives can increase the quantity and quality of maternal health services and address health systems and financial barriers that prevent women from accessing and providers from delivering quality, lifesaving maternal healthcare

Ring vaccination with rVSV-ZEBOV under expanded access in response to an outbreak of Ebola virus disease in Guinea, 2016: an operational and vaccine safety report.

BACKGROUND: In March, 2016, a flare-up of Ebola virus disease was reported in Guinea, and in response ring vaccination with the unlicensed rVSV-ZEBOV vaccine was introduced under expanded access, the first time that an Ebola vaccine has been used in an outbreak setting outside a clinical trial. Here we describe the safety of rVSV-ZEBOV candidate vaccine and operational feasibility of ring vaccination as a reactive strategy in a resource-limited rural setting. METHODS: Approval for expanded access and compassionate use was rapidly sought and obtained from relevant authorities. Vaccination teams and frozen vaccine were flown to the outbreak settings. Rings of contacts and contacts of contacts were defined and eligible individuals, who had given informed consent, were vaccinated and followed up for 21 days under good clinical practice conditions. FINDINGS: Between March 17 and April 21, 2016, 1510 individuals were vaccinated in four rings in Guinea, including 303 individuals aged between 6 years and 17 years and 307 front-line workers. It took 10 days to vaccinate the first participant following the confirmation of the first case of Ebola virus disease. No secondary cases of Ebola virus disease occurred among the vaccinees. Adverse events following vaccination were reported in 47 (17%) 6-17 year olds (all mild) and 412 (36%) adults (individuals older than 18 years; 98% were mild). Children reported fewer arthralgia events than adults (one [<1%] of 303 children vs 81 [7%] of 1207 adults). No severe vaccine-related adverse events were reported. INTERPRETATION: The results show that a ring vaccination strategy can be rapidly and safely implemented at scale in response to Ebola virus disease outbreaks in rural settings. FUNDING: WHO, Gavi, and the World Food Programme

The role of sex separation in neutral speciation

Neutral speciation mechanisms based on isolation by distance and sexual selection, termed topopatric, have recently been shown to describe the observed patterns of abundance distributions and species-area relationships. Previous works have considered this type of process only in the context of hermaphrodic populations. In this work we extend a hermaphroditic model of topopatric speciation to populations where individuals are explicitly separated into males and females. We show that for a particular carrying capacity speciation occurs under similar conditions, but the number of species generated decreases as compared to the hermaphroditic case. Evolution results in fewer species having more abundant populations.Comment: 18 pages + 8 figure